Open-source discovery of chemical leads for next-generation chemoprotective antimalarials

Author:

Antonova-Koch Yevgeniya1ORCID,Meister Stephan1ORCID,Abraham Matthew1ORCID,Luth Madeline R.1ORCID,Ottilie Sabine1,Lukens Amanda K.23ORCID,Sakata-Kato Tomoyo3ORCID,Vanaerschot Manu4ORCID,Owen Edward5ORCID,Jado Juan Carlos1,Maher Steven P.67ORCID,Calla Jaeson1ORCID,Plouffe David8,Zhong Yang8,Chen Kaisheng8,Chaumeau Victor910ORCID,Conway Amy J.67,McNamara Case W.8,Ibanez Maureen8ORCID,Gagaring Kerstin8,Serrano Fernando Neria11ORCID,Eribez Korina1ORCID,Taggard Cullin McLean1,Cheung Andrea L.1,Lincoln Christie1ORCID,Ambachew Biniam1ORCID,Rouillier Melanie12ORCID,Siegel Dionicio13,Nosten François910ORCID,Kyle Dennis E.67ORCID,Gamo Francisco-Javier12,Zhou Yingyao8,Llinás Manuel514ORCID,Fidock David A.4ORCID,Wirth Dyann F.23ORCID,Burrows Jeremy12ORCID,Campo Brice12ORCID,Winzeler Elizabeth A.113ORCID

Affiliation:

1. School of Medicine, University of California, San Diego, 9500 Gilman Drive 0760, La Jolla, CA 92093, USA.

2. Harvard T. H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.

3. The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.

4. Division of Infectious Diseases, Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.

5. Department of Biochemistry and Molecular Biology and Center for Malaria Research, Pennsylvania State University, University Park, PA 16802, USA.

6. Center for Tropical and Emerging Global Diseases, University of Georgia, 500 D. W. Brooks Drive, Athens, GA 30602, USA.

7. Department of Global Health, University of South Florida, 3720 Spectrum Boulevard, Tampa, FL 33612, USA.

8. The Genomics Institute of the Novartis Research Foundation, 10675 John J Hopkins Drive, San Diego, CA 92121, USA.

9. Shoklo Malaria Research Unit, Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.

10. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

11. Tres Cantos Medicines Development Campus, Malaria DPU, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.

12. Medicines for Malaria Venture, Post Office Box 1826, 20 Route de Pre-Bois, 1215 Geneva 15, Switzerland.

13. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive 0741, La Jolla, CA 92093, USA.

14. Department of Chemistry and Center for Infectious Diseases Dynamics, Pennsylvania State University, University Park, PA 16802, USA.

Abstract

A path to tackle liver-stage parasites Malaria parasites are evolutionarily prepared to resist drug attack. Resistance is emerging to even the latest frontline combination therapies, which target the blood stages of the Plasmodium parasite. As an alternative strategy, Antonova-Koch et al. investigated the possibilities of drugs against liver-stage parasites (see the Perspective by Phillips and Goldberg). To do so, they devised a luciferase-reporter drug screen for the rodent parasite Plasmodium berghei. Three rounds of increasingly stringent screening were used. From this regime, several chemotypes that inhibit Plasmodium mitochondrial electron transport were identified. Excitingly, several new scaffolds, with as-yet-unknown modes of action but solely targeting the parasites' liver stages, emerged as promising drug leads for further development. Science , this issue p. eaat9446 ; see also p. 1112

Funder

Bill and Melinda Gates Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3